Effects of green tea polyphenols on dopamine uptake and on MPP⁺-induced dopamine neuron injury

As antioxidants, polyphenols are considered to be potentially useful in preventing chronic diseases in man, including Parkinson's disease (PD), a disease involving dopamine (DA) neurons. Our studies have demonstrated that polyphenols extracted from green tea (GT) can inhibit the uptake of ³H-dopamine (³H-DA) and 1-methyl-4-phenylpyridinium (MPP⁺) by DA transporters (DAT) and partially protect embryonic rat mesencephalic dopaminergic (DAergic) neurons from MPP⁺-induced injury. The inhibitory effects of GT polyphenols on ³H-DA uptake were determined in DAT-pCDNA3-transfected Chinese Hamster Ovary (DAT-CHO) cells and in striatal synaptosomes of C57BL/6 mice in vitro and in vivo. The inhibitory effects on ³H-MPP⁺ uptake were determined in primary cultures of embryonic rat mesencephalic DAergic cells. Inhibition of uptake for both ³H-DA and ³H-MPP⁺ was dose-dependent in the presence of polyphenols. Incubation with 50 μM MPP⁺ resulted in a significant loss of tyrosine-hydroxylase (TH)-positive cells in the primary embryonic mesencephalic cultures, while pretreatment with polyphenols (10 to 30 μg/ml) or mazindol (10 μM), a classical DAT inhibitor, significantly attenuated MPP⁺-induced loss of TH-positive cells. These results suggest that GT polyphenols have inhibitory effects on DAT, through which they block MPP⁺ uptake and protect DAergic neurons against MPP⁺-induced injury.